The overall goal of this collaborative project between SibTech, Inc. (PI: Backer J.) and Johns Hopkins University (PI: Pomper M.) is clinical development of efficient and cost-effective anti-angiogenic 177Lu radiopharmaceutical, scV/Lu, for VEGF receptor mediated targeting of angiogenic tumor vasculature. Current very expensive anti-angiogenic compounds induce transient regression of tumor vasculature in some patients but cause only marginal if any improvement in overall survival in many cancer patients. Our data in mouse models of primary and metastatic breast cancer indicate that scV/Lu induces a sustainable vascular regression, inhibits growth of primary tumor and metastatic lesions, improves overall survival, and readily combines with front-line chemotherapy. scV is a proprietary recombinant single-chain vascular endothelial growth factor (scVEGF), engineered for site-specific derivatization with PEGylated chelators, which binds to and internalized by VEGF receptors with native affinity. In Phase I of this contract, using syngeneic mouse model of orthotopic breast cancer, we will establish if selective targeting of VEGFR-1 or VEGFR-2 with scV/Lu may provide additional therapeutic benefits and define our lead candidate for further development. In Phase II we will develop the lead scV/Lu candidate through late preclinical development (GMP production, dosimetry, toxicology) and undertake physician-initiated exploratory Phase I trial in cancer patients.